This proposal seeks funding to support and extend an interdisciplinary predoctoral program that prepares students with strong backgrounds in quantitative physical sciences to conceptualize, conduct, and direct independent research in molecular biophysics and structural biology. This Molecular Biophysics and Structural Biology (MBSB) program places a strong emphasis on interdisciplinary, collaborative research in an environment where the practical human health consequences of research are appreciated and contribute to guiding and driving basic research. The training faculty consists of 40 independent investigators spread over 14 departments within the School of Medicine and the Faculty of Arts and Sciences at the University of Pittsburgh and within Carnegie Mellon University. The training faculty comprises a large group of senior members who have strong records in graduate training, funding, and publication, and a smaller contingent of junior faculty who bring new ideas and technical expertise to the group. The research programs of training faculty emphasize not only characterization of biomolecular phenomena but also development of new methodologies. At every stage of the curriculum, emphasis is placed on the relationship between physical methods and biological understanding. The research is concentrated in core areas at the challenging forefront of biomolecular science, including membrane proteins, protein-protein interactions and oligomeric complexes, nucleic acid structure and protein-nucleic acid interactions, poorly structured protein elements, protein misfolding and aggregation, and small molecule ligand - protein interactions. The training program includes a first year core curriculum featuring an introduction to biophysical instrumentation and methods, how these are used to address specific molecular questions, an introduction to theory and simulation of biomolecular behavior, and courses on statistical analysis and computer programming. Student's abilities to synthesize and creatively utilize what they have learned in the classroom are tested in a qualifying exam that requires them to construct and defend a research proposal not related to their own laboratory work. After passing this exam students move on to develop and pursue their thesis project. Students are required to participate in a weekly journal/data club and to attend a Molecular Biophysics seminar series featuring invited local and national speakers. Students are also encouraged to participate in several local, annual science meetings. This application proposes special features new to the MBSB program including incentives to develop co-mentored, collaborative thesis projects and an annual mini-symposium, with significant student participation, set within the MBSB graduate program. Students are also encouraged to take advantage of the rich environment of the School of Medicine to attend seminars in molecular aspects of human disease. We are requesting funds to support six traineeships with the goal to train a new generation of molecular biophysicists who will be leaders in future efforts to understand normal and abnormal human biology at the physical and molecular level. PUBLIC HEALTH RELEVANCE: Future progress in the understanding and treatment of many diseases will require a thorough knowledge of the molecular and biophysical processes underlying normal and abnormal biology. This application proposes to support and strengthen a growing multi-disciplinary, multi-departmental graduate program in Molecular Biophysics and Structural Biology which will train students to conduct physical and molecular research in a medical school environment where collaborative, health related projects are encouraged.